I am having the same trouble with a 2 tb EXT3 HDD connected to either USB port on my 421e. The drive works fine on my LSWV4.0, but does not show up at all in the drive tab of the HTML interface. I am certain this is a bug in the 421e firmware, as (1) I replaced my first 421e with a second one, which has the same issue, and (2) tech support told me that the two ports are on different buses. The odds of having two defective units, with two defective port buses apiece, are about equal to the odds of being hit with lightning, I'd think.
One thing in the OP confuses me, though: i cannot get FAT32 USB sticks to show up at all in the interface drive tab. Another thing in the reply confuses me: How does one change sector size if the drive won't even show up on the drive list? I tried connecting an NTFS drive that I use with my PC, and it also failed to show up on the drive tab. Would I have to reformat the drive to 2k sector sizes on a PC rather than using the 421e drive tab interface?
In the OP's case, does the HDD show up in the drive tab but fail to operate or is it simply invisible to the firmware? As mentioned, it is the latter in my case, at least on NAS. (It does show up in drive management on the PC.)